High Resolution Multi-parametric Diagnostics and Therapy of Atrial Fibrillation: Chasing Arrhythmia Vulnerabilities in the Spatial Domain

After a century of research, atrial fibrillation (AF) remains a challenging disease to study and exceptionally resilient to treatment. Unfortunately, AF is becoming a massive burden on the health care system with an increasing population of susceptible elderly patients and expensive unreliable treatment options. Pharmacological therapies continue to be disappointingly ineffective or are hampered by side effects due to the ubiquitous nature of ion channel targets throughout the body. Ablative therapy for atrial tachyarrhythmias is growing in acceptance. However, ablation procedures can be complex, leading to varying levels of recurrence, and have a number of serious risks. The high recurrence rate could be due to the difficulty of accurately predicting where to draw the ablation lines in order to target the pathophysiology that initiates and maintains the arrhythmia or an inability to distinguish sub-populations of patients who would respond well to such treatments. There are electrical cardioversion options but there is not a practical implanted deployment of this strategy. Under the current bioelectric therapy paradigm there is a trade-off between efficacy and the pain and risk of myocardial damage, all of which are positively correlated with shock strength. Contrary to ventricular fibrillation, pain becomes a significant concern for electrical defibrillation of AF due to the fact that a patient is conscious when experiencing the arrhythmia. Limiting the risk of myocardial injury is key for both forms of fibrillation. In this project we aim to address the limitations of current electrotherapy by diverging from traditional single shock protocols. We seek to further clarify the dynamics of arrhythmia drivers in space and to target therapy in both the temporal and spatial domain; ultimately culminating in the design of physiologically guided applied energy protocols. In an effort to provide further characterization of the organization of AF, we used transillumination optical mapping to evaluate the presence of three-dimensional electrical substrate variations within the transmural wall during acutely induced episodes of AF. The results of this study suggest that transmural propagation may play a role in AF maintenance mechanisms, with a demonstrated range of discordance between the epicardial and endocardial dynamic propagation patterns. After confirming the presence of epi-endo dyssynchrony in multiple animal models, we further investigated the anatomical structure to look for regional trends in transmural fiber orientation that could help explain the spectrum of observed patterns. Simultaneously, we designed and optimized a multi-stage, multi-path defibrillation paradigm that can be tailored to individual AF frequency content in the spatial and temporal domain. These studies continue to drive down the defibrillation threshold of electrotherapies in an attempt to achieve a pain-free AF defibrillation solution. Finally, we designed and characterized a novel platform of stretchable electronics that provide instrumented membranes across the epicardial surface or implanted within the transmural wall to provide physiological feedback during electrotherapy beyond just the electrical state of the tissue. By combining a spatial analysis of the arrhythmia drivers, the energy delivered and the resulting damage, we hope to enhance the biophysical understanding of AF electrical cardioversion and xiii design an ideal targeted energy delivery protocol to improve upon all limitations of current electrotherapy

Clock Distribution Network Optimization by Sequential Quadratic Programing

Clock mesh is widely used in microprocessor designs for achieving low clock skew and high process variation tolerance. Clock mesh optimization is a very diffcult problem to solve because it has a highly connected structure and requires accurate delay models which are computationally expensive. Existing methods on clock network optimization are either restricted to clock trees, which are easy to be separated into smaller problems, or naive heuristics based on crude delay models. A clock mesh sizing algorithm, which is aimed to minimize total mesh wire area with consideration of clock skew constraints, has been proposed in this research work. This algorithm is a systematic solution search through rigorous Sequential Quadratic Programming (SQP). The SQP is guided by an efficient adjoint sensitivity analysis which has near-SPICE(Simulation Program for Integrated Circuits Emphasis)-level accuracy and faster-than-SPICE speed. Experimental results on various benchmark circuits indicate that this algorithm leads to substantial wire area reduction while maintaining low clock skew in the clock mesh. The reduction in mesh area achieved is about 33%

Economic and regulatory uncertainty in renewable energy system design: a review

Renewable energy is increasingly mobilizing more investment around the globe. However, there has been little attention to evaluating economic and regulatory (E&R) uncertainties, despite their enormous impact on the project cashflows. Consequently, this review analyzes, classifies, and discusses 130 articles dealing with the design of renewable energy projects under E&R uncertainties. After performing a survey and identifying the selected manuscripts, and the few previous reviews on the matter, the following innovative categorization is designed: sources of uncertainty, uncertainty characterization methods, problem formulations, solution methods, and regulatory frameworks. The classification reveals that electricity price is the most considered source of uncertainty, often alone, despite the existence of six other equally influential groups of E&R uncertainties. In addition, real options and optimization arise as the two main approaches researchers use to solve problems in energy system design. Subsequently, the following aspects of interest are discussed in depth: how modeling can be improved, which are the most influential variables, and potential lines of research. Conclusions show the necessity of modeling E&R uncertainties with currently underrepresented methods, suggest several policy recommendations, and encourage the integration of prevailing approaches.Peer ReviewedObjectius de Desenvolupament Sostenible::7 - Energia Assequible i No Contaminant::7.2 - Per a 2030, augmentar substancialment el percentatge d’energia renovable en el con­junt de fonts d’energiaObjectius de Desenvolupament Sostenible::7 - Energia Assequible i No ContaminantPostprint (published version

Advanced Air Bag Technology Assessment

As a result of the concern for the growing number of air-bag-induced injuries and fatalities, the administrators of the National Highway Traffic Safety Administration (NHTSA) and the National Aeronautics and Space Administration (NASA) agreed to a cooperative effort that "leverages NHTSA's expertise in motor vehicle safety restraint systems and biomechanics with NASAs position as one of the leaders in advanced technology development... to enable the state of air bag safety technology to advance at a faster pace..." They signed a NASA/NHTSA memorandum of understanding for NASA to "evaluate air bag to assess advanced air bag performance, establish the technological potential for improved technology (smart) air bag systems, and identify key expertise and technology within the agency (i.e., NASA) that can potentially contribute significantly to the improved effectiveness of air bags." NASA is committed to contributing to NHTSAs effort to: (1) understand and define critical parameters affecting air bag performance; (2) systematically assess air bag technology state of the art and its future potential; and (3) identify new concepts for air bag systems. The Jet Propulsion Laboratory (JPL) was selected by NASA to respond to the memorandum of understanding by conducting an advanced air bag technology assessment. JPL analyzed the nature of the need for occupant restraint, how air bags operate alone and with safety belts to provide restraint, and the potential hazards introduced by the technology. This analysis yielded a set of critical parameters for restraint systems. The researchers examined data on the performance of current air bag technology, and searched for and assessed how new technologies could reduce the hazards introduced by air bags while providing the restraint protection that is their primary purpose. The critical parameters which were derived are: (1) the crash severity; (2) the use of seat belts; (3) the physical characteristics of the occupants; (4) the proximity of the occupants to the airbag module; (5) the deployment time, which includes the time to sense the need for deployment, the inflator response parameters, the air bag response, and the reliability of the air bag. The requirements for an advanced air bag technology is discussed. These requirements includes that the system use information related to: (1) the crash severity; (2) the status of belt usage; (3) the occupant category; and (4) the proximity to the air bag to adjust air bag deployment. The parameters for the response of the air bag are: (1) deployment time; (2) inflator parameters; and (3) air bag response and reliability. The state of occupant protection advanced technology is reviewed. This review includes: the current safety restraint systems, and advanced technology characteristics. These characteristics are summarized in a table, which has information regarding the technology item, the potential, and an date of expected utilization. The use of technology and expertise at NASA centers is discussed. NASA expertise relating to sensors, computing, simulation, propellants, propulsion, inflatable systems, systems analysis and engineering is considered most useful. Specific NASA technology developments, which were included in the study are: (1) a capacitive detector; (2) stereoscopic vision system; (3) improved crash sensors; (4) the use of the acoustic signature of the crash to determine crash severity; and (5) the use of radar antenna for pre-crash sensing. Information relating to injury risk assessment is included, as is a summary of the areas of the technology which requires further development

The 1992 Research/Technology report

The 1992 Research & Technology report is organized so that a broad cross section of the community can readily use it. A short introductory paragraph begins each article and will prove to be an invaluable reference tool for the layperson. The approximately 200 articles summarize the progress made during the year in various technical areas and portray the technical and administrative support associated with Lewis technology programs

Aeronautical engineering: A continuing bibliography with indexes (supplement 304)

This bibliography lists 453 reports, articles, and other documents introduced into the NASA scientific and technical information system in May 1994. Subject coverage includes: design, construction and testing of aircraft and aircraft engines; aircraft components, equipment, and systems; ground support systems; and theoretical and applied aspects of aerodynamics and general fluid dynamics

An integrated study of earth resources in the State of California using remote sensing techniques

The author has identified the following significant results. The supply, demand, and impact relationships of California's water resources as exemplified by the Feather River project and other aspects of the California Water Plan are discussed

Observing giant panda habitat and forage abundance from space

Giant pandas are obligate bamboo grazers. The bamboos favoured by giant pandas are typical forest understorey plants. Therefore, the availability and abundance of understorey bamboo is a key factor in determining the quantity and quality of giant panda food resources. However, there is little or no information about the spatial distribution or abundance of bamboo underneath the forest canopy, due to the limitations of traditional ground survey and remote sensing classification techniques. In this regard, the development of methods that can predict the understorey bamboo spatial distribution and cover abundance is critical for an improved understanding of the habitat, foraging behaviour and distribution of giant pandas, as well as facilitating an optimal conservation strategy for this endangered species. The objectives of this study were to develop innovative methods in remote sensing and GIS for estimating the giant panda habitat and forage abundance, and to explain the altitudinal migration and the spatial distribution of giant pandas in the fragmented forest landscape. It was concluded that 1) the vegetation indices derived from winter (leaf-off) satellite images can be successfully used to predict the distribution of evergreen understorey bamboo in a deciduous-dominated forest, 2) winter is the optimal season for quantifying the coverage of evergreen understorey bamboo in a mixed temperate forest, regardless of the classification methods used, 3) a higher mapping accuracy for understorey bamboo in a coniferous-dominated forest can be achieved by using an integrated neural network and expert system algorithm, 4) the altitudinal migration patterns of sympatric giant pandas and golden takins are related to satellite-derived plant phenology (a surrogate of food quality) and bamboo abundance (a surrogate of food quantity), 5) the driving force behind the seasonal vertical migration of giant pandas is the occurrence of bamboo shoots and the temperature variation along an altitudinal gradient, 6) the satellite-derived forest patches occupied by giant pandas were significantly larger and more contiguous than patches where giant pandas were not recorded, indicating that giant pandas appear sensitive to patch size and isolation effects associated with forest fragmentation. Overall, the study has been shown the potential of satellite remote sensing to map giant panda habitat and forage (i.e., understorey bamboo) abundance. The results are important for understanding the foraging behaviour and the spatial distribution of giant pandas, as well as the evaluation and modelling of giant panda habitat in order to guide decision-making on giant panda conservation. <br/